Abstract
Lifestyle-induced weight loss is regarded as an efficient therapy to reverse metabolic syndrome (MetS) and to prevent disease progression. The objective of this study was to investigate whether lifestyle-induced weight loss modulates gene expression in circulating monocytes. We analyzed and compared gene expression in monocytes (CD14+ cells) and subcutaneous adipose tissue biopsies by unbiased mRNA profiling. Samples were obtained before and after diet-induced weight loss in well-defined male individuals in a prospective controlled clinical trial (ICTRP Trial Number: U1111-1158-3672). The BMI declined significantly (− 12.6%) in the treatment arm (N = 39) during the 6-month weight loss intervention. This was associated with a significant reduction in hsCRP (− 45.84%) and circulating CD14+ cells (− 21.0%). Four genes were differentially expressed (DEG’s) in CD14+ cells following weight loss (ZRANB1, RNF25, RB1CC1 and KMT2C). Comparative analyses of paired CD14+ monocytes and subcutaneous adipose tissue samples before and after weight loss did not identify common genes differentially regulated in both sample types. Lifestyle-induced weight loss is associated with specific changes in gene expression in circulating CD14+ monocytes, which may affect ubiquitination, histone methylation and autophagy.
Highlights
Lifestyle-induced weight loss is regarded as an efficient therapy to reverse metabolic syndrome (MetS) and to prevent disease progression
Our study addresses the question of whether lifestyle-induced weight loss modulates the gene expression of peripheral circulating blood monocytes in individuals with MetS who are at high risk for type 2 diabetes mellitus and cardiovascular disease (CVD)
We identified four protein coding genes in paired C D14+ samples of the treatment arm that were differentially expressed after the 6-month intervention period (Table 3) namely, ZRANB1, RNF25, RB1CC1 and KMT2C (Lysine Methyltransferase 2C; adj. p = 0.049, log fold change = − 0.20)
Summary
Lifestyle-induced weight loss is regarded as an efficient therapy to reverse metabolic syndrome (MetS) and to prevent disease progression. Adipose tissue is primarily composed of adipocytes and immune cells such as macrophages It has been increasingly recognized as a major source of circulating proinflammatory cytokines, which are typically observed in obesity-associated metabolic d ysfunction[1]. Lifestyle-induced weight loss significantly improves metabolic and cardiovascular outcomes in patients with MetS10 This suggests that the frequency and the gene expression profile of peripheral blood monocytes may change upon weight loss. Our study addresses the question of whether lifestyle-induced weight loss modulates the gene expression of peripheral circulating blood monocytes in individuals with MetS who are at high risk for type 2 diabetes mellitus and CVD. We analyzed and compared the gene expression profiles of paired CD14+ monocyte samples and corresponding adipose tissue samples before and after lifestyle-induced weight loss in well-defined individuals with MetS in a prospective controlled clinical trial (ICTRP Trial Number: U1111-1158-3672)
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